1. Gender differences in fetal growth have been reported, but it is unknown if fetal growth rates, a reflection of genetic and environmental factors, express sexually dimorphic sensitivity to the mother. Our group investigated the homogeneity of male and female growth responses to maternal height and weight in 3,495 uncomplicated singleton pregnancies (1,814 males, 1,681 females) followed longitudinally.(1) Gender modified the effects of maternal height and weight on fetal growth rates and birth weight. Among males, tallest maternal height influenced fetal weight growth before 18 weeks of gestation, and pre-pregnancy maternal weight and body mass index subsequently had influence;this finding was not seen in females. Additionally, males were more sensitive to maternal weight among shorter mothers and more responsive to maternal height among lighter mothers, compared to females. A male advantage of 60 g occurred among neonates of the shortest and lightest mothers, compared to 150 and 191 g among short and heavy mothers, and tall and light-weight mothers, respectively. This study concluded that gender differences in response to maternal size are under-appreciated sources of variation in fetal growth studies and may reflect differential growth strategies. 2. Iliac crest angle: a novel sonographic parameter for the prediction of Down syndrome risk during the second trimester of pregnancy. We investigated a new sonographic technique for the display and measurement of the fetal iliac crest angle (ICA) and determined its value estimating the risk of Down syndrome during the midtrimester.(2) Three-dimensional ultrasonography (3DUS) of the fetal pelvis was performed during genetic amniocenteses. Two different ICAs were measured from a coronal projection of the fetal pelvis. Axial inner (ICA-inner), middle (ICA-middle) and outer (ICA-outer) ICAs were also measured. Ninety-four normal fetuses and 19 fetuses with Down syndrome were examined. The ICA-middle and ICA-coronal 2 parameters were the most reproducible measurements. The mean ICA-middle measurement for fetuses with Down syndrome was significantly greater than that for normal subjects (94.5 vs. 83.1 degrees). The mean ICA-coronal 2 angle measurement for fetuses with Down syndrome was slightly greater than that for normal subjects (57.9 vs. 51.9 degrees). A multiple logistic regression model including ICA-middle and ICA-coronal 2 provided a predictive ability of 88.1%. This combination had a sensitivity of 94.4% for a false-positive rate of 5% in the detection of Down syndrome. We propose that standardized ICA measurements of the fetal pelvis can be used to identify some fetuses at risk for trisomy 21 during the midtrimester of pregnancy. 3. Evaluation of the soft tissue of fetal limbs with 3DUS is feasible. The use of fractional limb volume addresses the technical limitations of fetal weight estimation. Our group conducted a study(3) to determine the accuracy and precision of new fetal weight estimation models, based on fractional limb volume and conventional two-dimensional (2D) sonographic measurements during the second and third trimesters. A prospective cross-sectional study of 271 fetuses was performed using 3DUS and measuring biparietal diameter (BPD), abdominal circumference (AC) and femoral diaphysis length (FDL)-plus fractional arm volume (AVol) and fractional thigh volume (TVol) within 4 days of delivery. Weighted multiple linear regression analysis was used to develop modified Hadlock models and new models using transformed predictors that included soft tissue parameters for estimating birth weight. Six new models were very accurate, with mean percent differences not significantly different from zero. Model 3 (ln of BPD, AC and AVol) and Model 6 (ln of BPD, AC and TVol) provided the most precise weight estimations (random error=6.6% of actual birth weight) as compared with 8.5% for the best original Hadllock model and 7.6% for a modified Hadlock model. This study demonstrates that the precision of fetal weight estimation can be improved by adding fractional limb volume measurements to conventional 2D biometry. These new models may offer novel insight into the contribution of soft tissue development to weight estimation. 4. The use of magnetic resonance imaging (MRI) during pregnancy is increasing. Diffusion-weighted imaging (DWI) provides an image contrast that is based on the molecular motion of water - a process that can be altered by the presence of disease. The apparent diffusion coefficient (ADC) is based on these principles and reflects water movement within the tissue environment. We conducted a study(4) to develop a reproducible method for estimating the diffusion of water in human fetal lung tissue using DWI. A secondary objective was to determine the relationship of the ADCs in the fetal lung to menstrual age and total lung volume. Normal pregnant volunteers underwent MRI. Simple linear regression was performed with Pearson correlation coefficient. Inter- and intra-examiner bias and 95% limits of agreement (LOA) were determined. Forty-seven scans were performed at a mean of 29.2 weeks. The median coefficient of variation for ADC was 5.6%. No differences in ADC values were found between right and left lungs. Normally distributed ADC measurements were not significantly correlated with either total lung volume or menstrual age. The mean ADC value was 1.75. Mean intra-examiner bias was -0.15 and inter-examiner bias was 2.2. These findings suggest that ADC measurements of the fetal lung are reproducible between blinded examiners and are independent of menstrual age or lung volume.(4) 5. A sonographic short cervix (SCX) is the most powerful predictor of preterm delivery. We investigated the frequency and clinical significance of intra-amniotic inflammation IAI, amniotic fluid (AF) MMP-8 >23 ng/mL in a cohort of 47 asymptomatic women with a SCX ( <or = 15 mm) between 14-24 weeks.(5) We found intra-amniotic infection in 4.3% of patients. Among those with a negative AF culture, the prevalence of IAI was 22% and patients with a negative AF culture, but with IAI, had a higher rate of delivery within 7 days (40% vs 5.7%) and a shorter median diagnosis-to-delivery interval than those without IAI (18 vs 42 days).(5) Moreover, we investigated whether the risk of early spontaneous preterm delivery (sPTD) in asymptomatic women with a SCX changes as a function of gestational age at diagnosis.(6) This cohort study included 109 asymptomatic singleton pregnancies with a SCX at 14-24 weeks, who were stratified by gestational age at diagnosis. Women diagnosed with a SCX <20 weeks had a higher rate of sPTD at <28 weeks (77% vs. 31%) and at <32 weeks (81% vs. 48%), and a shorter median diagnosis-to-delivery interval (21 vs. 61.5 days) than those diagnosed at 20-24 weeks. The rate of amniotic fluid "sludge" was higher among patients diagnosed at <20 weeks than those diagnosed between 20-24 weeks (92% vs. 48%).(6) We further evaluated the pregnancy outcome of asymptomatic patients with a non-measurable cervical length (0 mm) between 14-28 weeks.(7) This retrospective cohort study included 78 patients with singleton pregnancies. We found that in 75% of the patients delivered <32 weeks of gestation, the median diagnosis-to-delivery interval was 20.5 days, and the delivery rate within 7 and 14 days was 28% and 36%, respectively. Patients with a non-measurable cervix diagnosed at <24 weeks had a shorter median diagnosis-to-delivery interval than those diagnosed between 24-28 weeks (17.5 vs 41 days).(7) These studies(5-7) demonstrate that a sonographic SCX in the midtrimester is a risk factor for preterm delivery and IAI, and that almost 65% of asymptomatic women with a 0 mm cervix in the second trimester will not deliver within 2 weeks, yet 75% of them will deliver before 32 weeks of gestation.